Endoglin and MMP14 contribute to Ewing sarcoma spreading by modulation of cell-matrix interactions
| العنوان: | Endoglin and MMP14 contribute to Ewing sarcoma spreading by modulation of cell-matrix interactions |
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| المؤلفون: | Pilar Puerto-Camacho, Juan Díaz-Martín, Joaquín Olmedo-Pelayo, Alfonso Bolado-Carrancio, Carmen Salguero-Aranda, Carmen Jordán-Pérez, Marina Esteban-Medina, Inmaculada Álamo-Álvarez, Daniel Delgado-Bellido, Laura Lobo-Selma, Joaquín Dopazo, Ana Sastre, Javier Alonso, Thomas G. P. Grünewald, Carmelo Bernabeu, Adam Byron, Valerie G. Brunton, Ana Teresa Amaral, Enrique De Álava |
| المساهمون: | European Commission, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Cáncer (España), Junta de Andalucía, Fundación CRIS contra el Cáncer, Asociación Candela Riera, Asociación Pablo Ugarte, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación María García Estrada, Universidad de Sevilla, Fundación Mari Paz Jiménez Casado, Grupo Español de Investigación en Sarcomas, Barbara and Wilfried Mohr Foundation, Todos somos Iván, Fundación LaSonrisaDeAlex, Puerto-Camacho, Pilar, Díaz-Martín, J., Salguero-Aranda, Carmen0000-0001-6010-8302, Alamo-Alvarez, Inmaculada0000-0002-6295-0218, Delgado-Bellido, Daniel0000-0002-9588-4747, Dopazo, Joaquín0000-0003-3318-120X, Alonso, Javier0000-0002-6287-8391, Bernabéu, Carmelo0000-0002-1563-6162, Byron, Adam0000-0002-5939-9883, Brunton, Valerie G. 0000-0002-7778-8794, Álava, Enrique de, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Fundación María García Estrada (Fundación MGE), Candela Ribera. Asociación contra el sarcoma de Ewing, Juan de la Cierva Incorporacion fellowship, University of Seville (España), Unión Europea. Fondo Social Europeo (ESF/FSE), Regional Government of Andalusia (España), CRIS contra el Cáncer, Asociación Pablo Ugarte contra el cáncer infantil, Asociación Todos somos Iván, Fundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing, Centro de Investigación Biomédica en Red - CIBERONC (Cáncer) |
| المصدر: | Puerto-Camacho, P, Díaz-Martín, J, Olmedo-Pelayo, J, Bolado-Carrancio, A, Salguero-Aranda, C, Jordán-Pérez, C, Esteban-Medina, M, Álamo-Álvarez, I, Delgado-Bellido, D, Lobo-Selma, L, Dopazo, J, Sastre, A, Alonso, J, Grünewald, T G P, Bernabeu, C, Byron, A, Brunton, V G, Amaral, A T & de Álava, E 2022, ' Endoglin and MMP14 contribute to Ewing sarcoma spreading by modulation of cell-matrix interactions ', International Journal of Molecular Sciences, vol. 23, no. 15, 8657 . https://doi.org/10.3390/ijms23158657 International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8657 Puerto-camacho, P, Olmedo-Pelayo, J, Bolado Carrancio, A, Salguero-aranda, C, Jordan-perez, C, Esteban-medina, M, Alamo-alvarez, I, Delgado-Bellido, D, Lobo-Selma, L, Dopazo, J, Sastre, A, Alonso-García, J, Grünewald, T G P, Bernabeu, C, Byron, A, Brunton, V G, Diaz-Martin, J, Amaral, A T & De Álava, E 2022, ' Endoglin and MMP14 contribute to Ewing sarcoma spreading by modulation of cell-matrix interactions ', Molecular Oncology . https://doi.org/10.3390/ijms23158657 |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Proteomics, Organic Chemistry, Endoglin/genetics, Endoglin, Bone Neoplasms, Mechano-transduction, General Medicine, Sarcoma, Ewing, Extracellular matrix, Bone Neoplasms/genetics, Sarcoma, Ewing/pathology, Ewing sarcoma, endoglin, mechano-transduction, extracellular matrix, Catalysis, Computer Science Applications, Inorganic Chemistry, Matrix Metalloproteinase 14, Matrix Metalloproteinase 14/genetics, Humans, Receptors, Growth Factor, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Signal Transduction |
| الوصف: | Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease. E.A.’s laboratory is supported by ISCIII-FEDER (PI20/00003), CIBERONC (CB16/12/00361), PAIDI-Junta de Andalucía (P18-RT-735), Fundación CRIS Contra el Cáncer, Asociación Candela Riera and Asociación Pablo Ugarte. A.T.A. is supported by Juan de la Cierva Incorporación fellowship (IJC-2018-036767-I); P.P.-C. is sponsored by the Fundación María García Estrada. J.O.-P is supported by Ph.D. Grant Plan Propio from the University of Seville. J.D.-M is supported by CIBERONC (CB16/12/00361). C.S.-A. is supported by the European Social Fund and the Junta de Andalucía (Talento Doctores 2020, DOC_01473). This work was supported by grants from the Consejería de Salud (Junta de Andalucía, grants No PI-0036-2017, PI-0040-2017, and PI-0061-2020) awarded to J.D.-M, A.T.A. and C. S.-A., respectively. This work was also supported by the GEIS-Fundación Mari Paz Jiménez Casado (IV beca trienal) granted to J.D.-M, the 13ª GEIS-Beca Buesa granted to A.T.A. and CRIS (Cancer Research Innovation Spain) granted to J.D.-M and E.A. The laboratory of T.G.P.G. is supported by the Barbara and Wilfried Mohr Foundation. The lab of J.A. is supported by the Instituto de Salud Carlos III (ISCIII), grant number PI20CIII/00020; Asociación Pablo Ugarte, grant numbers TRPV205/18, TPI-M 1149/13; Asociación Candela Riera; Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant reference: TVP333-19. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b14f3fdd59e619a8e554921049ba6d3 https://research.manchester.ac.uk/en/publications/35b6e2b3-87a4-47a4-bb41-d7c0f52f0dc2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1b14f3fdd59e619a8e554921049ba6d3 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |